American Association for the Advancement of Science 2009 Fighting the Rising Tide of Antibiotic Resistance: Causes and Cures in the Sea Friday February 13 3:30 – 5:00 PM, Chicago, IL Symposium Organizer and Moderator Carolyn Sotka, NOAA's Oceans and Human Health Initiative, Charleston, SC Senior Science-Policy Analyst NOAA's Oceans and Human Health Initiative Hollings Marine Laboratory 331 Fort Johnson Road Charleston, SC 29412-9110 Phone: 843-817-5971 Fax: 843-762-8737 Symposium Co-Organizer Paul Sandifer, NOAA's Oceans and Human Health Initiative, Charleston, SC NOS Senior Scientist for Coastal Ecology NOAA's Oceans and Human Health Initiative Hollings Marine Laboratory 331 Fort Johnson Road Charleston, SC 29412-9110 Phone: 843-762-8814 Fax: 843-762-8737 paul.sandifer@noaa.gov Virulent bacteria are winning the arms race against our current arsenal of antibiotic drugs, posing a significant and growing threat to global public and ocean health. In the United States, diseases and secondary infections related to antibiotic resistance are on the rise, difficult to treat, cost in excess of 5 billion dollars annually and may account for more deaths than from HIV-AIDS, Parkinson's disease, emphysema or homicide. Research has turned to the ocean to provide insight about potential causes and cures in this evolutionary battle. Methicillin-resistant Staphylococcus aureus (MRSA) has been detected and isolated from coastal waters and beaches, and resistance patterns in bacteria that commonly cause seafood illness have been discovered. The presence of these bacteria in coastal environments may increase the exposure of humans to resistant infections, increase the potential for new, stronger strains to emerge and prevent common treatment. At the same time, marine natural products researchers are discovering new ways to potentially render out-of-use antibiotics effective again, find novel drugs and help fight the resistance war. In this symposium, an interdisciplinary panel of government, academic and non-profit scientists will present the latest research on the spreading, strengthening, and evolution of antibiotic resistance in the ocean, and promising new solutions and treatments from undersea medicine cabinets. MRSA’s Silent Threat: What happens at the beach doesn’t always stay at the beach Lisa R W Plano1, Anna C Garza1, Helena M Solo-Gabriele1, Cristina Ortega1, Lora E Fleming1, and Jay M Fleisher2 University of Miami1 and Nova Southeastern University2 Staphylococcus aureus is a common commensal bacterium found colonizing humans, their pets and thriving in the environment. In addition to peaceful coexistence with humans, these bacteria are capable of causing numerous types of serious infections when given the opportunity. S. aureus are responsible for infections ranging from simple infections of the middle ear to those of the blood, bones and major organs. Adding to the challenges faced in treating staphylococcal infections; these organisms have acquired resistance to virtually all antibiotics used against them. Infections with S. aureus, and especially the multi-drug resistant MRSA, have become responsible for huge healthcare costs and are projected to be responsible for more deaths this year than HIV/Aids. The serious health threat posed by S. aureus is not limited to the hospitals or healthcare setting as acquired infections from community sources are emerging as a significant threat. In fact, infections by MRSA are now the most common cause of skin and soft tissue ailments in people who go to the nation’s emergency rooms for care. As infections with these organisms increase, the search for all the sites or sources where they may survive and be shared among individuals is paramount. By determining the locations where the bacteria are harbored and the factors that may contribute to spreading these bacteria, plans can be devised to decrease the spread and therefore the risk. Our studies investigate a popular marine recreational beach as a potential reservoir for MRSA to be shared by those individuals using these waters. Our hypothesis is that the bathers using recreational waters not only contribute to the organisms in the water, and therefore serve as a source of pathogens, but might also become colonized or infected by the organisms that they are exposed to while in the water or on the beaches. In the first large epidemiology study investigating potential pathogens at a beach not impacted by sanitary sewage discharges, 1303 adult habitual bathers were randomly assigned to bather or non-bather groups, with subsequent follow-up for reported illness and environmental sampling of indicator organisms and potential pathogens. S. aureus, including MRSA, were isolated from the water associated with 37% (2.7% MRSA) of the bathers during recreational use. Additional studies using marine waters in small and large pool settings confirmed that bathers, both adults and young children in diapers, were a source of S. aureus and MRSA isolated from the study waters and sand samples. These findings support our hypothesis and demonstrate that human health risks occur in non-point source recreational marine beaches. Lisa R. W. Plano, M.D., Ph.D. Associate Professor Departments of Pediatrics, Microbiology & Immunology and Dermatology Leonard M. Miller School of Medicine University of Miami 1600 NW 10Th Ave Miami, Fl 33136 (305) 243-2598 office (305) 243-4623 fax chroma.med.miami.edu/micro/faculty_plano_l.html lplano@miami.edu Uncovering Patterns of Antibiotic Resistance in Seafood-borne Pathogens Abstract: The spread of antibiotic resistance (AR) among pathogenic microorganisms is a major public health concern and a striking example of evolution in action. What remains largely unknown is the environmental origins of AR and the natural and human-induced controls of AR in the environment. Many microbial genes responsible for AR are millions of years old. They became a public health concern only recently, after the introduction of antibiotics to treat human and livestock pathogens. The use and abuse of antibiotics has resulted in a dramatic selection for and subsequent proliferation of pathogens carrying antibiotic resistance genes. Other chemical agents, including toxic metals, may also be indirectly involved in the selection for AR, through genetic linkages of multiple resistance factors. Some AR genes are located on mobile genetic elements, enabling their transfer among various microbial species. In the largest survey of its kind, we found that resistances to all major classes of antibiotics are prevalent in Vibrio vulnificus, V. parahaemolyticus, and E. coli along the southeastern U.S. Atlantic coast. Numerous Vibrios were resistant to antibiotics routinely prescribed to treat their infections, including tetracyclines, aminoglycosides, and cephalosporins. V. vulnificus causes 95% of all seafood poisoning-related deaths in the U.S. The fatality rate approaches 100% if not appropriately treated within 72 hours. Our results emphasize the significance of environmental AR studies and may lead to improved treatment of seafood-borne infections. We demonstrated that industrial effluents containing toxic metals may induce selection for AR in freshwater environments. We did not observe the same effects in marine environments, e.g. the frequency of AR in Vibrios was similar in pristine and metal-contaminated coastal areas. This is likely due to lower metal toxicity in seawater relative to freshwater. However, water and sediment samples collected near urban centers contained E. coli with elevated AR, indicating prolonged survival of resistant strains originating from municipal effluents. We obtained the complete genome of one multi-resistant E. coli strain with extreme AR. The genome sequence revealed multiple cellular mechanisms governing AR, including novel genes as well as genes encoded on mobile genetic elements. The genetic signature of this bacterium suggests that it was transported into the study area by migrating birds. Our results demonstrate the importance of complex ecosystem processes in the proliferation of AR in opportunistic human pathogens in the environment. Ramunas Stepanauskas Senior Research Scientist Bigelow Laboratory for Ocean Sciences P.O. Box 475 West Boothbay Harbor, Maine 04575-0475 Phone: 207-633-9600 Mobile: 207 380 4688 Fax: 207-633-9641 e-mail: rstepanauskas@bigelow.org homepage: http://www.bigelow.org/srs/stepanauskas.html Breaking the Barrier: Discovery of Anti-Resistance Factors and Novel Ocean Drugs Abstract: National Oceanic and Atmospheric Administration (NOAA)’s investigations into coral disease, red tides and other marine environmental issues have led to discoveries of novel chemicals as a source for new pharmaceuticals. A class of these chemicals function as antibiotics for microorganisms providing survival advantages and may be applied for use in human health care. Our research has found several compounds such as euglenophycin, recently isolated and characterized from Euglena sanguinea (a freshwater and estuarine microbe) which exhibits very strong antibiotic, antifungal, and antiviral potential as well as some anti-cancer and angiogenesis activities. Also, our research into coral disease has resulted in thousands of new bacterial isolates producing highly selective antimicrobial compounds such as in the Gorgonian coral Pseudopterogoria americana that yields highly selective small peptide antibiotics. Many of these novel anti-biotics are advantageous, as they demonstrate no cytotoxic responses to human cells and may minimize negative side effects associated with those drugs in current usage. Observations from the sponge Agelas conifera’s ability to protect itself against fouling and disease led to the discovery of ageliferin isolates that demonstrate very strong anti-biofilm activity. The compounds with this specific activity hold promise to increase the efficacy of current and out of use antibiotics with their ability to inhibit and/or disperse the protective layer that infectious agents often produce to protect themselves. Such compounds are also finding potential use in other areas of human health as well, including cystic fibrosis, chemo-therapy, antifungal agents, and for use in medical stints and prosthetics. Marine natural products hold much promise in combating both the trend of antibiotic resistance but also to discover new antibiotics. The one-two punch of discovering new antibiotics as well as novel chemicals that make older generation drugs more effective represents cutting edge science addressing a critical need in human health care. Peter Moeller, Ph.D. Toxin/Natural Products Chemistry Program National Ocean Service Center of Excellence for OHH at the Hollings Marine Laboratory 331 Ft. Johnson Road Charleston, SC 29412 peter.moeller@noaa.gov (843) 762-8867 Fax: 843-762-8737